TSPYL5 induces cancer stem cells stemness by G3BP1/RanBP2-mediated p53 modification in Neuroblastoma
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE223866 | GEO | 2025/01/06
REPOSITORIES: GEO
Similar Datasets
Project description:TSPYL5 induces cancer stem cells stemness by G3BP1/RanBP2-mediated p53 modification in Neuroblastoma
| PRJNA928702 | ENA
Project description:Stress granules (SGs) are stress-induced membraneless organelles whose dynamics are tightly regulated by protein interactions and modifications. However, whether SUMOylation directly targets SG core proteins G3BP1/2 and which ligase is involved remains unclear. Capturing these key events while preserving SG integrity is challenging due to their transient and membraneless nature. To address this, we introduce a low-concentration formaldehyde crosslinking (lcFAX) method that stabilizes membraneless organelles, including G3BP1 SGs and TDP-43 nuclear bodies, enabling enhanced proteome identification. Importantly, we identify TRIM28 as a previously undefined SG-associated protein and reveal that TRIM28 SUMOylates G3BP1 at K287 and G3BP2 at K281, establishing a critical mechanism regulating SG dynamics that ultimately impacts cellular ROS and apoptosis. lcFAX-Seq also provides insights into the RNA composition of SGs. Altogether, lcFAX-MS uncovers the critical role of TRIM28-mediated SUMOylation in modulating SG dynamics, establishing lcFAX as a powerful tool for analyzing membraneless organelles and the underlying regulatory mechanisms.
2025-09-24 | GSE286197 | GEO
Project description:Mitochondrial calcium signaling plays a critical role in mitochondrial homeostasis during non-alcoholic steatohepatitis (NASH) progression. Here, we report Ras‐GTPase activating protein SH3 domain‐binding protein 1 (G3BP1), a core protein of stress granule (SG), significantly upregulated in NAFLD/NASH patients, mouse models and palmitic acid-stimulated hepatocytes. Hepatocyte-specific G3BP1 deficiency attenuates NASH in two dietary mouse models. SG and the mitochondrial import protein TOM70 collaboratively mediate the translocation of G3BP1 to the mitochondria. G3BP1 interacts and stabilizes mitochondrial calcium uptake 1 (MICU1) via inhibiting YME1L1-mediated degradation of MICU1, and also impedes MCU complex activity and assembly, leading to mitochondrial calcium overload. Moreover, metabolic stress suppresses TRIM25-mediated K63-ubiquitination of G3BP1 and subsequent SG disassembly. Pharmacological inhibition of G3BP1 impairs the G3BP1-MICU1 interaction and prevents mitochondrial homeostasis imbalance and NASH progression. Collectively, we uncover the significant role of mitochondrial G3BP1 in mitochondrial homeostasis and NASH progression, which provides a potential target for therapeutic interventions.
2024-08-18 | GSE274650 | GEO
Project description:Mitochondria regulate cellular processes through direct and indirect interactions with other organelles. A well-studied example is contact with the endoplasmic reticulum at mitochondrial-associated ER membranes (MAMs), which control pathways including redox and calcium homeostasis. Recent studies also reported direct mitochondria–nuclear membrane contacts in cancer cells and yeast that promote pro-survival signaling, but how exchange occurs across two largely impermeable membranes remains unclear. Here, we describe the existence of direct interactions between the nuclear pore and the mitochondria. In two unbiased proteomic screens, GST pulldown and BioID, VDAC1 was the top mitochondrial candidate that interacts with the nuclear pore protein RANBP2. In vitro RANBP2 CRISPR knock-out, RANBP2 truncation, or site directed mutagenesis of RANBP2-interacting amino acids in VDAC1 resulted in reduced mitochondria-nucleus proximity and decreased nuclear ATP and phosphocreatine levels. This was accompanied by a decline in levels of the nuclear phosphoproteome, and downregulation of pathways involved in histone modification, cellular differentiation and transcriptional regulation in vitro. We show differential ATAC peaks in Ranbp2 Wildtype and knockout cells in 10T1/2. Moreover, deletion of RANBP2 C-terminal domain in vivo in mice resulted in embryonic lethality due to cardiac and neural crest differentiation defects. Collectively, these results describe a mechanism by which mitochondria directly interact with the NPC, a phenomenon which is critical for regulation nuclear energetics and cellular differentiation during embryonic development.
2026-03-17 | GSE324952 | GEO
Project description:Mitochondria regulate cellular processes through direct and indirect interactions with other organelles. A well-studied example is contact with the endoplasmic reticulum at mitochondrial-associated ER membranes (MAMs), which control pathways including redox and calcium homeostasis. Recent studies also reported direct mitochondria–nuclear membrane contacts in cancer cells and yeast that promote pro-survival signaling, but how exchange occurs across two largely impermeable membranes remains unclear. Here, we describe the existence of direct interactions between the nuclear pore and the mitochondria. In two unbiased proteomic screens, GST pulldown and BioID, VDAC1 was the top mitochondrial candidate that interacts with the nuclear pore protein RANBP2. In vitro RANBP2 CRISPR knock-out, RANBP2 truncation, or site directed mutagenesis of RANBP2-interacting amino acids in VDAC1 resulted in reduced mitochondria-nucleus proximity and decreased nuclear ATP and phosphocreatine levels. This was accompanied by a decline in levels of the nuclear phosphoproteome, and downregulation of pathways involved in histone modification, cellular differentiation and transcriptional regulation in vitro. We show differential H3K27me3 histone epigenetic landscape in Ranbp2 Wildtype and knockout cells in 10T1/2. Moreover, deletion of RANBP2 C-terminal domain in vivo in mice resulted in embryonic lethality due to cardiac and neural crest differentiation defects. Collectively, these results describe a mechanism by which mitochondria directly interact with the NPC, a phenomenon which is critical for regulation nuclear energetics and cellular differentiation during embryonic development.
2026-03-17 | GSE324951 | GEO
Project description:TRIM28-Mediated SUMOylation of G3BP1/2 Regulates Stress Granule Dynamics
| PRJNA1208106 | ENA
Project description:we identify G3BP1 as a novel rG4-binding protein, and reveal that G3BP1 can modulate mRNA stability through its binding with rG4 structures
2021-03-16 | GSE168943 | GEO
Project description:To investigate whether G3BP1 binds to telomeric DNA, we performed the ChIP-seq analysis of G3BP1 in KGN cells.
2024-04-14 | GSE263539 | GEO
Project description:RNA-Seq was performed upon protein depletion to examine whether the loss of RanBP2, Nup88 or Nup214 contributes to transcriptional changes.
2020-06-15 | GSE133177 | GEO
Project description:Speckle-type POZ protein (SPOP), an E3 ubiquitin ligase, acts as a tumor suppressor. We identified G3BP1 as non-substrate interactor of SPOP. G3BP1 is a well-known oncogene in many cancer types, but its role in prostate cancer (PCa) remains largely elusive. We showed that G3BP1 functions as an upstream regulator and potent endogenous inhibitor of Cul3SPOP, suggesting a distinctive Cul3SPOP inactivation independent of SPOP mutations. Transcriptomic analysis together with functional studies revealed that the G3BP1-SPOP ubiquitin signaling axis is involved in PCa progression through activating AR signaling. Further, AR upregulates G3BP1 to potentiate feed-forward amplification of signaling through G3BP1-SPOP axis. Overall, we show G3BP1high PCa tumors constitute a new subset where G3BP1 inhibits Cul3SPOP function to upregulate AR signaling, and promotes tumorigenesis.
2021-09-26 | GSE138612 | GEO